Serotonin, the Endothelium and the Coronary Circulation

Summary

Serotonin releases endothelium-derived relaxing factors and also causes contraction of vascular smooth muscle cells. The latter may be important at sites of damaged endothelium and promote thrombus formation and vasospasm. In epicardial porcine coronary arteries, endothelium-dependent relaxations to serotonin are impaired by the inhibitor of nitric oxide formation L-N^G-monomethyl arginine (L-NMMA). Since pertussis toxin reduces endothelium-dependent relaxations to serotonin, a pertussis toxin sensitive G protein is involved. In intramyocardial porcine coronary arteries, L-NMMA is a weak inhibitor of the endothelium-dependent relaxation to serotonin and pertussis toxin has no effect. Thus, the importance of nitric oxide as well as that of pertussis toxin sensitive G protein decreases from large to small porcine coronary arteries.

In epicardial porcine coronary arteries, oxidized, but not native LDL inhibit endothelium-dependent relaxations to serotonin in a dose-dependent manner. As the relaxations to the nitric oxide donor SIN-1 are completely maintained, a reduced vascular responsiveness to endothelium-derived nitric oxide can be excluded. In contrast to serotonin, the endothelium-dependent relaxations to bradykinin are unaffected by oxidized LDL. As the same inhibitory pattern is obtained with inhibitors of endothelium-derived nitric oxide, the effect of oxidized LDL appears to be related to a reduced production and/or release of the endogenous nitrate. This may promote platelet aggregation and vasospasm, both known clinical events in patients with coronary artery disease.

In human left anterior descending coronary arteries, threshold and low concentrations of endothelin-1 potentiate contractions to serotonin. As the production of endothelin-1 by endothelial cells is stimulated by thrombin, this effect of the peptide may contribute to the vasospastic events associated with platelet aggregation.